YM758

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

YM758 是一种 If 电流通道抑制剂。

YM758 is an inhibitor of If current channel.(In Vitro):YM758 inhibits rOct1- (IC50 = 23.8 μM) and hOCT1- (IC50 = 40.5 μM) mediated [3H]MPP uptake in a concentration-dependent manner. YM758 inhibits OATP1B1-mediated [3H]E217βG uptake in a concentration-dependent manner(IC50 = 13.0 μM). YM758 shows no inhibitory effect on OATP1B3-mediated [3H]E217βG uptake.(In Vivo):In tachycardia-induced dogs, YM758 (0.03, 0.1, and 0.3 mg/kg; i.v.) plasma concentrations rapidly decrease with t1/2s of 1.62, 4.93, and 1.63 h, respectively. The CLtot values are1.71, 1.69, and 1.48 L/h/kg, and Vdss values amount to 3.19, 5.78, and 2.94 L/kg accordingly. The radioactivity in the rat eyeballs after dosing 14C-YM758 is extracted. The radioactivity recovery is 97.1% at 4 h and 67.1% at 24 h. In the eyeball at 4 h after administration, YM758 (the unchanged drug) is the main compound detected (66.7%).

The inhibitory effect of YM758 on [3H]MPP uptake via human/rat organic cation transporters (hOCT1/rOct1) is investigated. YM758 inhibits rOct1- and hOCT1-mediated [3H]MPP uptake in a concentration-dependent manner with IC50 values of 23.8 and 40.5 μM, respectively. The IC50 value of YM758 for [14C]Metformin uptake via rOct1 may be estimated below 10 μM in the same way, whereas that is much smaller than that for [3H]MPP uptake. In addition, the inhibitory effect of YM758 on [3H]E217βG uptake via OATP1B1 and OATP1B3 is investigated. YM758 inhibits OATP1B1-mediated [3H]E217βG uptake in a concentration-dependent manner with a IC50 value of 13.0 μM. YM758 has no inhibitory effect on OATP1B3-mediated [3H]E217βG uptake.

After a single intravenous administration of 0.03, 0.1, and 0.3 mg/kg to tachycardia-induced beagles, YM758 plasma concentrations rapidly decrease with t1/2 values of 1.62, 4.93, and 1.63 h, respectively. At the corresponding doses, the CLtot values amount to 1.71, 1.69, and 1.48 L/h/kg, and Vdss values are 3.19, 5.78, and 2.94 L/kg, respectively. Because the plasma concentration 24 h after administration is quantified only in the 0.1 mg/kg dosing group, the larger values of t1/2 and Vdss are obtained compared with those in other dosing groups. The PK profile of YM758 in tachycardia-induced dogs appeares to be linear within the dose range of 0.03 to 0.3 mg/kg. The CLtot of YM758 in the blood basis (CLb,dog) is estimated to be 1.47 to 1.69 L/h/kg. The radioactivity in the rat eyeballs after dosing 14C-YM758 is extracted with a mixture of 2 mol/L hydrochloric acid and Methanol (5:95, v/v); the radioactivity recovery is 97.1% at 4 h and 67.1% at 24 h. The HPLC recovery of radioactivity from the extracted samples is 90.6 and 100.6% at 4 and 24 h, respectively. In the eyeball at 4 h after administration, YM758 (the unchanged drug) is the main compound detected (66.7%), and the metabolites YM-252124 (14.5%), YM-394111 (2.4%), and YM-234903 (1.8%) are also observed.

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Others

Other Targets

Anti-infection| Fungal

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312752-85-5

469.55

C26H32FN3O4

>98% (HPLC)

In Vitro:?DMSO : 100 mg/mL (212.97 mM)

C(=O)(N1CC=2C(=CC(OC)=C(OC)C2)CC1)[C@H]3CN(CCNC(=O)C4=CC=C(F)C=C4)CCC3

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(-20℃)

With Ice Pack

≥ 2 years